Skip to main content
European Commission logo
English English
CORDIS - EU research results
CORDIS

Deciphering the Role of aberrant glycOSylation in the rEsponse to Targeted TherApies for breast cancer

Project description

Role of aberrant glycosylation in targeted breast cancer therapy

Therapy resistance leading to cancer progression is a major obstacle to successful treatment. The development of targeted therapies such as trastuzumab has revolutionised the treatment of patients with human epidermal growth factor receptor 2 positive (HER2+) breast cancer. Aberrant glycosylation of proteins has been linked to multiple processes including invasion, angiogenesis and modulation of the immune response. The HER2 receptor is heavily glycosylated, and it is the target of current antibody-based treatments, including trastuzumab. The research goal of the EU-funded ROSETTA project is to decipher the role of glycosylation in developing resistance to HER2-targeted therapies. The project has the potential to identify new markers of response to therapies and find new therapeutic options for the improvement of current treatments.

Objective

Resistance and cancer progression remain a major obstacle to the successful treatment of cancer. In HER2+ breast cancer, the development of targeted therapies such as trastuzumab, has revolutionized the treatment for these cancer patients. However, a significant number of patients develop resistance. In this realm, my previous work focused on understanding the crosstalk of interconnected signaling pathways in HER2+ cancer cells that drive tumorigenesis and undermine the efficacy of current treatments.
The research goal of this proposal is to provide a new focus to the challenge of resistance by deciphering the role of glycosylation in driving resistance to HER2-targeted therapies. Aberrant glycosylation of proteins is a hallmark in cancer and has been linked to multiple processes such as invasion, angiogenesis and modulation of the immune response. The receptor HER2, the main driver of HER2+ cancers, is heavily glycosylated and is the target of current antibody-based treatments, including trastuzumab. In this scenario, this proposal aims to (1) identify glycosylation-related genes associated with incomplete pathological response to trastuzumab to (2) dissect their role on trastuzumab binding and (3) assess their impact in the response to trastuzumab mediated by immune cells. This research plan will be accomplished combining the analysis of clinical data from tumor biopsies, the use of trastuzumab-resistant tumor-derived breast cancer cell lines and, the implementation and imaging of 3D heterotypic cultures of cancer cell line-derived spheroids and immune cells. Thus, this proposal addresses a largely unexplored layer of complexity in cancer biology – the role of glycosylation in resistance to targeted therapies – and holds the potential to identify new markers of response to therapies and open the path to new therapeutic options for the improvement of current treatments.

Coordinator

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
Net EU contribution
€ 175 572,48
Address
DR MOLEWATERPLEIN 40
3015 GD Rotterdam
Netherlands

See on map

Region
West-Nederland Zuid-Holland Groot-Rijnmond
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 175 572,48